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We have read with great interest the letters by Sacchetti et al. and Bellone et al. As stated in the introduction of our article, it was also the impression of all physicians in our institution involved in the care of patients with pulmonary edema that BiPAP is indeed helpful in its treatment. However, as is the case in many other treatment modalities, sometimes the clinical impression does not hold in the face of rigorous randomized studies. Therefore, we have tried in the discussion part of our manuscript to suggest a few mechanisms to explain the failure of BiPAP in our patient population. What was especially alarming to us was that the results in the BiPAP arm were worse than our previous experience with simple medical therapy (without high-dose nitrates). Accordingly, we decided to discontinue the study prematurely.
Regarding the remarks by Sacchetti et al. and Bellone et al.: Firstly, it is possible that some of the harmful effect we observed was due to combination of BiPAP ventilation with morphine (although it will be very hard from an ethical point of view to deny patients this small amount of morphine, which is a proven treatment for pulmonary edema). Secondly, we have chosen BiPAP rather than CPAP for our study because BiPAP has some advantage over CPAP by increasing the tidal volume. Also, it was our subjective impression that patients tolerate BiPAP better than CPAP. Thirdly, regarding the BiPAP pressures used in our protocol, it is possible that the moderate pressures we used in the BiPAP arm were not enough and higher pressures would have produced a better effect. However, from our experience, it seemed to us that patients usually do not tolerate higher pressures. Hence, we started with lower pressures and increased the pressures gradually. Furthermore, again taking into account that these two treatment arms were not compared directly, it seems that the patients in the BiPAP arm of our study faired worse than our historical controls that underwent exactly the same treatment without BiPAP. If the assumption of Sacchetti et al. and Bellone et al. were correct, then we would expect that the results of the BiPAP arm would be the same as conservative treatment (basically, if we administered too little BiPAP it should be the same as administering a lot of oxygen only).
Regarding the pH and PCO2measurements suggested by Bellone et al., these were not performed, because the treatment was administered at the patients’ homes by paramedic units, which are not equipped for such measurements.
Finally, regarding the early CK peak induced by BiPAP, we are not aware of any randomized study demonstrating this event. However, the negative results in our study included not only high CK but also an increased rate of mechanical ventilation, lower O2saturation, and increased total events. Furthermore, what we have observed was that in the BiPAP arm more patients had an increase in CK into the MI range. In the others we did not observe a CK increase at all. Therefore, we believe that this cannot be explained by early CK release, because the patients who did not have an MI did not have CK release at all.
Since the publication of our study, another randomized study comparing BiPAP ventilation, with conservative treatment using oxygen, morphine, furosemide and low-dose nitrates, was published (1). In this study, the outcome of patients treated by BiPAP ventilation was better than in the control arm, although the study was small (as was our study) and there were significant inequalities in baseline parameters between the two groups. Therefore, we believe that the resolution of this important issue will need further, larger randomized studies.
- American College of Cardiology